RRC ID 88116
Author Haque R, Setty H, Lorenzo R, Stelzer G, Rotkopf R, Salzberg Y, Goldman G, Kumar S, Halber SN, Leifer AM, Schneidman E, Laurent P, Oren-Suissa M.
Title Decoding sexual dimorphism of the sex-shared nervous system at single-neuron resolution.
Journal Sci Adv
Abstract Sex-specific behaviors are often attributed to differences in neuronal wiring and molecular composition, yet how genetic sex shapes the molecular architecture of the nervous system at the individual neuron level remains unclear. Here, we use single-cell RNA sequencing to profile the transcriptome of sex-shared neurons in adult Caenorhabditis elegans males and hermaphrodites. We uncover widespread molecular dimorphism across the nervous system, including in previously unrecognized neuron-types such as the touch receptors. Neuropeptides and signaling-related genes exhibit strong sex-biased expression, particularly in males, reinforcing the notion that neuropeptides are crucial for diversifying connectome outputs. Despite these differences, neurotransmitter identities remain largely conserved, indicating that functional dimorphism arises through modulatory, not identity-defining, changes. We show that sex-biased expression of neurotransmitter-related genes correlates with bias in outgoing synaptic connectivity and identify regulatory candidates for synaptic wiring, including both shared and sex-specific genes. This dataset provides a molecular framework for understanding how subtle regulatory differences tune conserved circuits to drive sex-specific behaviors.
Volume 11(28)
Pages eadv9106
Published 2025-7-11
DOI 10.1126/sciadv.adv9106
PMID 40644535
PMC PMC12248294
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Female Gene Expression Profiling Male Nervous System* / metabolism Neurons* / metabolism Neuropeptides / genetics Neuropeptides / metabolism Sex Characteristics* Single-Cell Analysis Transcriptome
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